Salsolinol (6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoneline;SAL) is a natural derivative of dopamine. It has been reported that alcohol consumption increases the level of SAL. While R-SAL is formed from enzymatic condensation of dopamine with pyruvic acid, non-enzymatic condensation of dopamine with acetaldehyde, the oxidation product of ethanol, generates the racemic mixture of (R,S)-SAL in vivo. To test a possibility of SAL representing a marker for alcohol addiction, a reliable method for quantification of the (S)-SAL stereo isomer from biological matrices was being established during this report period. To improve the sensitivity and stability of the SAL stereoisomer analysis, a new approach using pentafluorobenzyl (PFB) derivatization is being explored. By optimizing derivatization procedures, SAL was derivatized fully at hydroxyl and the secondary amine groups and analyzed by electrospray ionization mass spectrometry in conjunction with chiral HPLC. The base line separation of the stereoisomers was achieved with pg level of detection sensitivity.